The assessment and treatment of psychiatric symptoms in persons with cognitive dysfunction are becoming increasingly important. Prevalence estimates of dementia in the United States range from 5% in those aged 71 to 79 years to 25% to 50% in those 90 or older. Up to 90% of patients with dementia have psychiatric comorbidities.1,2

Physicians who treat patients with dementia must remember that dementia is not merely a problem with memory. The presence of one or more additional cognitive disturbances, including aphasia, apraxia, or agnosia, is required to make the diagnosis according to DSM-IV-TR criteria. Furthermore, some patients may present with changes in personality or deficits in executive function rather than memory impairment, which complicates the initial diagnosis.3 Additional mental and behavioral disturbances often affect patients and caregivers as much as memory deficits and may influence quality of life, the need for institutionalization, mortality, and caregiver burden.2,4,5

This article emphasizes neuropsychiatric disturbances with the greatest prevalence and morbidity in persons with dementia. It also addresses comorbid depressive and anxiety disorders, as well as psychological and behavioral disturbances associated with dementia—psychosis and agitation/aggression.3,6

DEPRESSIONDepression affects 20% to 32% of persons with dementia: the prevalence is higher in patients with vascular dementia than in patients with Alzheimer disease (AD).6 Assessing depression in dementia patients poses several challenges. Depressive symp­toms can be the initial manifestations of dementia and may fluctuate over time.2,3 Compared with older patients with intact cognition, patients with dementia are more likely to report a diminished ability to concentrate or indecisiveness during a major depressive episode.4 On the other hand, patients with dementia are less likely to report insomnia/hypersomnia, feelings of worthlessness and guilt, or thoughts of death/suicide.4

To account for these differences, revised diagnostic criteria have been proposed for depression in patients who have AD. Specifically, participants in the NIMH Depression of Al­zheimer Disease Workshop suggested adding irritability, social with­draw­al, and isolation.7,8

Further confounders of assessment include symptoms of apathy and anxiety. These symptoms frequently coexist with depression but are also independent behavioral dimensions.9

Several measures are available for screening and diagnosing depression. In the early stages of the disease, the Geriatric Depression Scale, which relies on patient self-report, can be used.10 In more advanced stages, clini­cian-administered instruments, such as the Hamilton Ratings Scale for Depression or the Cornell Scale for Depression in Dementia, are more practical. Both have been validated in patients with broad ranges of cognitive impairment.11,12

Treatment of depressionA variety of approaches can be used to treat depression in patients with dementia. These include electroconvulsive therapy (ECT), pharmcotherapy, and psychosocial modalities.

Antidepressants. Although placebo-controlled studies of antidepressants have produced contradictory results, the American Psychiatric Association (APA) practice guidelines support a trial of an antidepressant to treat clinically significant depressive symptoms in patients with dementia.2,3 SSRIs are generally first-line agents because they have a better safety and tolerability profile than tricyclic antidepressants or mono­amine oxidase inhibitors, which have cardiovascular and anticholinergic adverse effects. Among the SSRIs, citalopram and sertraline appear to have an edge in efficacy based on limited clinical trials. They may also be preferable because they are least likely to induce or inhibit cytochrome P-450 enzymes and interact with other drugs.2,3

Alternative agents, including serotonin norepinephrine reuptake inhibitors (venlafaxine, duloxetine), mirtazapine, and buproprion, may be second-line treatment options. However, data from controlled studies are lacking. Patients with dementia are particularly prone to medication adverse effects; whichever agent is chosen, the paradigm of “start low and go slow” should be followed.

ECT. If pharmacological interventions are not effective or contraindicated, ECT can be considered. Risks (including high rates of delirium in dementia patients) and benefits (including improved cognition when depression is successfully treated) must be carefully weighed on an individual basis.2

Psychosocial modalities. Nonpharmacological interventions include supportive-therapy techniques, such as reminding the patient of earlier accomplishments, focusing on positive aspects of life, instilling hope, and promoting enjoyable recreational activities.13 Of 11 randomized controlled studies of psychosocial treatments of depression in older adults with dementia, 7 showed significant improvement in the treatment group compared with the control group. In 6 of these studies, improvements were maintained beyond the active treatment.14

The psychosocial treatments studied were diverse. They included interventions based on behavioral approaches that focus on training care­­givers to problem-solve and com­municate effectively. Structured pro- pro­­­grams were used to increase social engagement, and interventions were employed to modify sensory or environmental stimulation.14 Group reminiscence therapy also improved cognitive and affective function in a recent randomized controlled trial undertaken by Wang.15

ANXIETYCommunity prevalence of anxiety in patients with dementia is nearly 20%.6 Generalized anxiety disorder (GAD), one of the most frequently diagnosed anxiety disorders in later life, occurs in 5% of patients with AD; estimates of clinically significant anxiety are as high as 70%, depending on the clinical sample (higher for vascular and frontotemporal dementias) and screening modality (lower in studies that employed structured clinical interviews).16-19

As with depression, the assessment of anxiety disorders in individuals with dementia is challenging. First, geriatric patients tend to underreport psychological problems and overemphasize somatic complaints.20 Another issue is the high comorbidity of anxiety with major depression in AD (more than 75%): this statistic raises the question of whether AD is independent from, or an epiphenomenon of, depression.16,17

A paucity of data validates criteria for anxiety disorders for patients with dementia. Findings from a study of GAD in patients with dementia indicate that restlessness, irritability, muscle tension, fear, and respiratory symptoms of anxiety significantly correlate with excessive anxiety and worry. Difficulty in concentrating, fatigue, and sleep disturbance do not.17 No studies to date have examined anxiety disorders other than GAD in this population.

Two instruments are available to specifically evaluate anxiety in dementia patients, although both correlate highly with measures of depression.21 The Worry Scale relies on self- report and can be used in patients with mild dementia.22 The Rating Anxiety in Dementia scale is based on information from all available sources, including clinical observation and caregiver reports; it has excellent reliability.23